Patients with advanced chronic joint inflammation suffer from severe joint deterioration including bone and cartilage destruction, resulting in long-term pain, deformity, loss of joint function, reduced mobility and shortened life expectancy. Joint inflammation is associated with an increased number of cells and inflammatory substances in the joint, which cause irritation, wearing down of cartilage and swelling of the joint lining. Several different autoimmune disorders are known to trigger inappropriate or misdirected inflammation in a joint, resulting in chronic inflammation in the joints of individuals who suffer from these disorders. Common inflammatory joint disorders include rheumatoid arthritis, psoriatic arthritis, Reiter's syndrome and ankylosing spondylitis.
Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and is estimated to affect approximately 1 percent of the U.S. population, or about 2.1 million Americans. RA is a chronic disease that is characterized by inflammation of the lining, or synovium, of the joints, and can lead to significant bone and cartilage damage over time. RA is more common in women than in men and as many as 3% of women may develop rheumatoid arthritis in their lifetime. Currently, the cause of RA is unknown.
RA can lead to long-term joint damage, resulting in chronic pain, loss of function and disability. In addition, recent research indicates that people with RA, particularly those whose disease is not well controlled, may have a higher risk for heart disease, stroke and the development of fibrosis, particularly lung fibrosis.
Lung fibrosis, including idiopathic pulmonary fibrosis and radiation-induced fibrosis, as well as fibrosis caused by smoking, chemical exposure, scleroderma, sarcoidosis, therapeutic radiation, RA, or lupus, afflicts 5,000,000 patients worldwide, and over 500,000 individuals in the U.S. The 5-year mortality from idiopathic pulmonary fibrosis is approximately 80%, accounting for 40,000 deaths per year in the U.S. alone. There currently is no approved therapy for idiopathic pulmonary fibrosis in the U.S. or Europe.
Thus, fibrosis and chronic joint inflammation caused by RA and other inflammatory conditions are international health burdens. There is a need to develop new agents for the prevention and treatment of these and other disorders.